Predicting Risk for Rapid Progression of ADPKD

ERA 60^th Congress

Patients with autosomal dominant polycystic kidney disease (ADPKD) commonly develop end-stage kidney disease (ESKD). ADPKD is characterized by the progressive development of bilateral renal cysts, which results in enlargement of the kidney volume, hypertension, and ESKD.

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The ERK-NET [European Rare Kidney Disease Reference Network] recently published a position paper outlining indications for the use of tolvaptan for the treatment of patients with ADPKD based on three algorithmic criteria: (1) total kidney volume and the Mayo Clinic Imaging Class (MCIC); (2) rate of decline in estimated glomerular filtration rate (eGFR); and (3) the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score, combining clinical and genetic variables. The MCIC and PROPKD scores are alternatively used to identify patients at risk for rapid progression of disease.

Valeria Aiello and colleagues conducted a retrospective, multicenter cohort study to examine and improve the concordance of sensitivity and specificity of MCIC and PROPKD predictive abilities for rapid disease progression. Results were reported at the ERA 60th Congress in a presentation titled Evaluation of the Predictive Ability and Concordance of Prognostic Scores for Rapid Progression in ADPKD: A Multicenter Cohort.

The study utilized data on adult patients with ADPKD from three renal centers (Bologna, Italy; Dublin, Ireland; and Berlin/Leipzig, Germany). Rapid disease progression was defined as eGFR slope ≥3 mL/min/1.73 m² per year over 4 years (clinical score), or MCIC classes 1C-D-E (imaging score), or high-risk PROPKD score (7-9 points). Clinical parameters were summarized using descriptive statistics. Kappa statistics were used to assess the concordance between MCIC and PROPKD scores.

In participants with PKD1 missense variants, the REVEL score was obtained and treated as a continuous variable. Scores greater than 0.65 were considered pathogenic and regarded as PKD1-truncating variants for PROPKD score calculation.

The cohort included 298 patients with ADPKD. Following 4 years of follow-up, results of multivariate analysis demonstrated significant associations between disease progression and MCIC (P=.041), hypertension (P=.031). and urologic events (P<.001). Assessment of rapid disease progression using PROPKD and MCIC scores yielded kappa of Cohen of 0.149; 47.9% (n=143) were concordant, and  49.32% (n=148) patients identified as rapid progressor for MCIC were identified as nonrapid progressor for PROPKD. Seven patients (2.3%) considered rapid progressor using PROPKD score were considered nonrapid progressor using MCIC classes.

Following reclassification of PKD1 missense variants by REVEL score, kappa of Cohen improved to 0.174 and PROPKD became predictive of fast progression (P=.01).

In conclusion, the researchers said, “Concordance between scores results [were] low (kappa of Cohen, 0.149). The PROPKD is more selective compared with the Mayo. Nevertheless, PROPKD allows the identification of some rapid progressor patients excluded from using the Mayo score only. The combined use of scoring may increase the ability to identify progressive patients. REVEL score could improve the agreement.”

Source: Aiello V, Elhassan E, Cristalli C, et al. Evaluation of the predictive ability and concordance of prognostic scores for rapid progression in ADPKD: a multicenter cohort. Presentation #55496. Abstract of a presentation at the European Renal Association 60th Congress; June 15-18, 2023; Milan, Italy.